Duchenne's muscular dystrophy

Question 1

what is DMD?

Answer 1

severe form of muscular dystrophy
low chance of survival past adolescence
affects skeletal muscles initially and then goes on to affect the heart and diaphragm
inherited condition

Question 2

pattern of inheritance of DMD?

Answer 2

x-linked recessive condition

Question 3

what are the causes of DMD?

Answer 3

almost entirely passed on by female carriers as affected males do not normally survive to reproduce

Question 4

epidemiology

Answer 4

1 in 3500 males

most common of the muscular dystrophies

Question 5

how is DMD diagnosed?

Answer 5

positive gower's test 
raised creatinine kinase in serum 
EMG - detects muscle destruction rather than problems with nerve conduction 
genetic testing
muscle biopsy 
LFTs - ALT and AST

Question 6

genetic testing

Answer 6

Xp21 defect

Question 7

when is DMD diagnosed?

Answer 7

between 5-5.5 years old

Question 8

what are the symptoms of DMD?

Answer 8

progressive proximal muscle weakness and wasting - most obvious = thigh 
calf swelling 
swelling of tongue 
developmental delay 
abnormal gait - difficulty standing 
trouble getting up from chairs
unable to walk upstairs
waddling gait
general motor skill deficits 
skeletal deformity 
unable to walk by 10 - need wheelchair 
cardiomyopathy

Question 9

what causes calf swelling?

Answer 9

pseudohypertrophy

Question 10

what causes swelling of the tongue?

Answer 10

fat replacement of wasted muscle

Question 11

cardiomyopathy in DMD

Answer 11

heart enlargement causing dilated cardiomyopathy

Question 12

what are the symptoms of dilated cardiomyopathy?

Answer 12

arrhythmia
shortness of breath
fatigue
leg and feet swelling

Question 13

what are the treatments for DMD?

Answer 13

corticosteroids 
physiotherapy 
mechanical ventilation at later stages 
physical aids 
occupational therapy 
ataluren 
creatine supplements 
gastrostomy 
ACE inhibitors and beta blockers for cardiomyopathy 
pacemaker
corrective surgery 
trial treatments
stem cell therapy

Question 14

corticosteroids

Answer 14

aggressive use sometimes before 10 can convert Duchenne’s to a more Becker’s like prognosis

Question 15

purpose of physio

Answer 15

reduces rate of contracture and prolongs the useful life of the muscles

Question 16

physical aids

Answer 16

wheelchair
leg braces
crutches

Question 17

ataluren

Answer 17

newer drug

for over 5s that can still walk

Question 18

what do creatine supplements do?

Answer 18

improve muscle strength

Question 19

what is corrective surgery used for?

Answer 19

scoliosis
ptosis
contractures
scapular fixation

Question 20

trial treatment

Answer 20

exon skipping

Question 21

what could stem cell therapy do?

Answer 21

regenerated damaged muscle tissue

Question 22

pathogenesis

Answer 22

mutation on DMD gene causes lack of dystrophin production, without it there is an excessive calcium entry into the cells, resulting in excess oxidative stress within the cells, damaging the sarcolemma and causing cell death

Question 23

what does dystrophin do?

Answer 23

part of a structure that connects the cytoskeleton of each muscle fibre to the basal lamina.

Question 24

why does a raised creatine kinase indicate DMD?

Answer 24

creatine kinase is found within skeletal muscles, brain tissue and cardiac muscle and so it leaks out when muscle cells are damaged as they are broken open and contents are released into the bloodstream

Question 25

what is the process of genetic testing for DMD?

Answer 25

genetic counselling
blood or saliva sample 
check dystrophin gene
CGH array testing 
MLPA testing 
PCR 
southern blot testing 
sanger gene sequencing 
can be done prenatally

Question 26

prenatal genetic testing

Answer 26

non-invasive prenatal diagnosis
chorion villus sampling 
amniocentesis
placental biopsy 
foetal blood sampling

Question 27

MLPA

Answer 27

multiplex ligation-dependent probe amplification

Question 28

CGH

Answer 28

comparative genomic hybridisation

Question 29

genetic testing

Answer 29

prenatal if parents are carriers
needed if you are offered genetic test
can be directed to relevant patient support groups
genetic testing is free if you are referred for it by a hospital specialist
discussion about risk, prognosis, consequences, tests available